The following aspects of the retinal vascular and pigment epithelial portions of the blood-retinal barrier will be investigated in normal and diabetic animals, intially rats: 1. topography and degree of barrier breakdown (vitreous fluorophotometry, fluorescein angiography, freeze-drying and fluorescence microscopy; 2. pore size and pathway of leakage (fluorescein labeled dextran, ultrastructural tracers: horseradish peroxidase, microperoxidase, lanthanum); 3. substructure of junctions (freeze-fracturing, in retinal pigment epithelium only); 4. distribution of microfilaments and their relationship to junctions (high voltage electron microscopy); 5. nature of microfilaments (decoration with myosin subfragment-1, high voltage electron microscopy); 6. distribution and diversity of gap junctions (lanthanum inpregnation, high voltage electron microscopy). The differential susceptibility of the normal and diabetic barrier to pharmacologic manipulation (Cytochalasin B, Prostaglandin E2, histamine) will be tested. The barrier will be disrupted experimentally (retinal ischemia, osmotic stress, acute hypertension), and both breakdown and especially repair of the barrier, will be studied. Experiments which lead to significant findings will be repeated in normal and diabetic dogs and monkeys. Retinal capillary basement membrane width will be assessed morphometrically, and its site of production and its permeability will be examined. Aspects 2 to 6 will also be studied in intra- and preretinal blood vessels of man (autopsy eyes of diabetic patients).